lenvatinib plus tislelizumab and capeox as first-line treatment for advanced gc/gejc with positive pd-l1 and low tmescore

Conditions: Gastric Cancer

Summary: this is a multicenter, prospective, phase ii clinical study to evaluate the efficacy and safety of intensive treatment with lenvatinib plus tislelizumab and capeox as first-line treatment for advanced gastric cancer or gastroesophageal junction adenocarcinoma with pd-l1 positive and low tmescore. a total of 92 subjects are randomly divided into study group and control group according to 1:1 ratio. tislelizumab 200mg, iv, d1+ oxaliplatin 130mg/m2, iv, d1+ capecitabine 1000mg/m2, bid po, d1-14, q3w ± lenvatinib 8mg, qd po regimen are received, respectively (3 weeks as a cycle, a maximum of 8 cycles of treatment). then the maintenance treatment phase with tislelizumab ± lenvatinib is entered, and the specific dosage is the same as the treatment period. effectiveness is assessed every 9 weeks (±7 days) until disease recurrence, metastasis, death, or loss of follow-up. the primary endpoint of this study was pfs, and secondary endpoints were os, orr, dor, and dcr.


Eligibility criteria:
inclusion criteria: 1. patients voluntarily participated in the study, signed the informed consent, and had good compliance; 2. age over 18 (including 18 years old), gender is not limited; 3. histologically and/or cytologically confirmed advanced gastric cancer or gastroesophageal junction adenocarcinoma (stage iv); 4. tumor with pd-l1 positive and low tumor microenvironment score (tmescore) 5. have not received systemic antitumor therapy before; or have previously received adjuvant or neoadjuvant therapy (chemotherapy/radiotherapy) for the purpose of cure, and the time of tumor recurrence \> 6 months since the last treatment 6. ecog performance status of 0-2 points; 7. expected survival ≥12 weeks; 8. blood test (without blood transfusion within 14 days) 1) neutrophil absolute value ≥1.5×10\^9/l, platelet ≥100×10\^9/l, hemoglobin ≥90g/l); 2) liver function test (aspartate aminotransferase and glutamate aminotransferase ≤3×uln, bilirubin ≤1.5×uln; in case of liver metastasis, ast and alt≤5×uln); 3) renal function (serum creatinine ≤1.5×uln, or creatinine clearance (ccr)≥60ml/min); 9. men and women of childbearing age must use effective contraceptive methods. exclusion criteria: 1. previously received therapy that targets t cell co-stimulation or checkpoint pathways ,such as anti-pd-1 antibodies, anti-pd-l1 antibodies, anti-ctla-4 antibodies, etc.; 2. previously received anti-vascular small-molecule targeted drug therapy, such as fuquinitinib, regofenib, etc.; 3. received major surgery within 4 weeks prior to the first drug administration; radiotherapy, radiofrequency ablation and other investigational drugs for tumors within 2 weeks; 4. received live vaccine within 4 weeks prior to the first drug administration (except inactivated viral vaccine for seasonal influenza); 5. a history of severe intolerance to drugs involved in the study (i.e., grade 4 toxicity of one of these drugs; class 3-4 toxicity of other co-administered drugs is not excluded); 6. known allergy to the study drug or any of its excipients; 7. her2 positive gastric cancer or gastroesophageal junction adenocarcinoma; 8. the patient had other malignancies within the previous 5 years or at the same time (except cured basal cell carcinoma, stage i squamous cell carcinoma, in situ carcinoma, intramucosal carcinoma, and superficial bladder cancer); 9. known brain or meningeal metastases; 10. patients who are preparing for or have previously received an organ or bone marrow transplant; 11. a history of human immunodeficiency virus (hiv) infection; 12. a history of psychotropic substance abuse or drug use; 13. condition that may interfere with the detection and management of suspected drug-related pulmonary toxicity, such as interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severe impairment of lung function; 14. known active or suspected autoimmune disease (except for patients with stable disease at enrollment who do not require systemic immunosuppressive therapy); 15. patients who required systemic corticosteroids (\> 10 mg/ day efficacy dose of prednisone) or other immunosuppressive agents within 2 weeks prior to initial administration or during the study period. however, adrenal hormone replacement therapy with topical or inhaled steroids, or a therapeutic dose of prednisone ≤ 10mg/ day in the absence of active autoimmune disease was permitted; 16. any active infection that requires systematic anti-infective treatment occurs within 2 weeks prior to the first dose (expect prophylactic antibiotic therapy, such as for urinary tract infections or chronic obstructive pulmonary disease); 17. active heart disease, including myocardial infarction, severe/unstable angina in the 6 months prior to treatment. echocardiography showed that the left ventricular ejection fraction was less than 50%, indicating poor arrhythmia control. 18. obvious clinical bleeding symptoms or obvious bleeding tendency and hemoptysis within 3 months prior to treatment. or treatment of venous/venous thrombosis events within the preceding 6 months, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism; long-term anticoagulant therapy with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day) is required; 19. any other disease, a clinically significant metabolic abnormality, abnormal physical examination or abnormal laboratory examination, for which, in the investigator's judgment, there is reason to suspect that the patient has a disease or condition unsuitable for the use of the investigational agent; 20. anything that, in the investigator's opinion, could put subjects receiving the study drug at risk, interfere with the study drug, subject safety assessment, or interpretation of the results; 21. pregnant or lactating women or women who may become pregnant.

Keywords: lenvatinib tislelizumab first-line treatment gc/gejc tme score pd-l1 positive